DE19738855C2 - Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer - Google Patents

Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer

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Publication number
DE19738855C2
DE19738855C2 DE1997138855 DE19738855A DE19738855C2 DE 19738855 C2 DE19738855 C2 DE 19738855C2 DE 1997138855 DE1997138855 DE 1997138855 DE 19738855 A DE19738855 A DE 19738855A DE 19738855 C2 DE19738855 C2 DE 19738855C2
Authority
DE
Germany
Prior art keywords
layer
transdermal therapeutic
therapeutic system
range
characterized
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
DE1997138855
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German (de)
Other versions
DE19738855A1 (en
Inventor
Thomas Hille
Lothar Deurer
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
LTS Lohmann Therapie Systeme GmbH and Co KG
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LTS Lohmann Therapie Systeme GmbH and Co KG
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by LTS Lohmann Therapie Systeme GmbH and Co KG filed Critical LTS Lohmann Therapie Systeme GmbH and Co KG
Priority to DE1997138855 priority Critical patent/DE19738855C2/en
Publication of DE19738855A1 publication Critical patent/DE19738855A1/en
Application granted granted Critical
Publication of DE19738855C2 publication Critical patent/DE19738855C2/en
Anticipated expiration legal-status Critical
Application status is Expired - Fee Related legal-status Critical

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Classifications

    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7038Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer
    • A61K9/7046Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds
    • A61K9/7053Transdermal patches of the drug-in-adhesive type, i.e. comprising drug in the skin-adhesive layer the adhesive comprising macromolecular compounds obtained by reactions only involving carbon to carbon unsaturated bonds, e.g. polyvinyl, polyisobutylene, polystyrene
    • A61K9/7061Polyacrylates
    • AHUMAN NECESSITIES
    • A61MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61KPREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES
    • A61K9/00Medicinal preparations characterised by special physical form
    • A61K9/70Web, sheet or filament bases ; Films; Fibres of the matrix type containing drug
    • A61K9/7023Transdermal patches and similar drug-containing composite devices, e.g. cataplasms
    • A61K9/703Transdermal patches and similar drug-containing composite devices, e.g. cataplasms characterised by shape or structure; Details concerning release liner or backing; Refillable patches; User-activated patches
    • A61K9/7084Transdermal patches having a drug layer or reservoir, and one or more separate drug-free skin-adhesive layers, e.g. between drug reservoir and skin, or surrounding the drug reservoir; Liquid-filled reservoir patches

Description

The invention relates to a transdermal therapeutic System (TTS), in particular a patch containing active ingredients, comprising a removable protective layer, an adhesive practicing reservoir layer as well as - if necessary adhesive overcoated - backing.

A TTS is an application to be applied to the skin form for active ingredients to be released via the skin that see traditional pavement. It's from one topical plasters containing active ingredients - for example one Rheumatism plasters or a corn plaster - too under divorce. Such a TTS can have one or more active ingredients fe contained continuously at a predetermined rate given at the application site for a specified period of time be. ("Heilmann, Klaus: Therapeutic Systems - Concept and implementation of programmed medicinal products chung ", 4th edition, 1984, Ferdinand-Enke-Verlag, Stuttgart cook). Usually the above is fixed set period 24 hours. For the treatment of chroni diseases is a long-term dose of Drugs required. It can therefore make sense a TTS also over a period of several days apply, as this tends to lead to constant plasma levels leads.

A typical such transdermal therapeutic system stem in the form of a plaster is for example from the EP B 0 430 019 known. This has an impermeable substance back layer, an adhesive reservoir layer and a removable protective layer. The active ingredient  permeable backing can be made of flexible or not fle xiblem material exist.

As substances used to manufacture such materials are used are polymer foils or metal foils or also a composite material made of a vapor-coated with aluminum Slide mentioned. Are such TTS ge longer on the skin wear like this - as mentioned above - for treatment of chronic diseases in particular is necessary due to the relative rigidity of the TTS, a pronounced foreign on the skin within a short time body feeling. This is extremely uncomfortable for the user take.

Another embodiment of such a TTS is described in example in US-A 5,246,705. The transdermal system described there has an elastomeric backing layer which has a defined vapor permeability in the range from 0.1 to 20 g / m 2 / h and a Young's modulus in the range from about 10 -1 to 10 4 N / cm 2 having. Particularly preferred materials for the elastomeric backing are, for example, ABA block copolymers, the A blocks being styrene and the B blocks being saturated hydrocarbon copolymers such as ethylene-butylene, ethylene-propylene copolymers and the like. acts. Even when the transdermal therapeutic systems according to the mentioned US Pat. No. 5,246,705 are worn for a long time on the skin, the described foreign body feeling cannot be avoided.

EP-A1 0 379 044 describes a flexible and water vapor permeable backing for TTS. There are no hints point to a particularly suitable range of elasticity or on the need for the elasticity of the backing to be observed within certain limits. The extensibility  should only be large enough to accommodate the movements of the Balance skin.

DE-PS 27 33 549 discloses a perforated, microporous This adhesive product for surgical purposes, which in any direction is stretchable. The stretchable or stretchable limit is given as 70 to 90%. DE-OS 16 67 944 describes a process by which tissue underlay elasticity for adhesive plasters, plaster bandages etc. can be generated in one direction by either the warp threads or the weft threads made of elastic crimp crepe yarn are made. The crimp crepe yarn used can be stretched elastically to 50-100% of its length. Use of such a base as a backing TTS is not provided. Because there are also natural fibers may contain it due to its microbial degradability in the intended use to an undesirable microbial germ growth are coming.

US Pat. No. 5,225,199 describes active substance patches, the one Have polyester film layer in two directions is stretchy. This film layer is not the back layer of the patch.

A strip-shaped wound bandage is known from US Pat. No. 4,780,168 known for sealing wounds from a woven or non-woven material based on a polymer is made, this material a planar Strec kung characteristic in the range of 0.88 to 192 N / cm has. Materials with such extensibility are but not readily as materials for back layers suitable for transdermal therapeutic systems. Either its elasticity is too low, then it turns up the unpleasant foreign body when worn on the skin for a long time perplexity; but if they are stretchy enough, then kick in the production of transdermal therapeutic sy  stemen the so-called "bowl formation" effect, the successor will be explained.

When making the laminate from which the individual acts material-containing plasters are punched, the material gets for the back layer under tension, and that here by resulting elastic restoring force leads to the fact that when punching the plasters, the opposite one another Ends are bent up. This effect leads to production due to the resulting rejects high costs combined with unnecessary environmental pollution.

Apart from the disadvantages mentioned, a material is for the back layer of a wound bandage for other reasons, like the required impermeability to active ingredients, not suitable for a TTS.

The object of the invention is therefore a transdermal to provide a therapeutic system that a re removable protective layer, a pressure-sensitive adhesive reservoir layer and a backing layer, optionally coated with an adhesive includes that avoids the disadvantages mentioned above. In particular, should wear for a long time, also over a days up to 1 to 2 weeks, no foreign body sensation adjust the skin. In addition, the manufacture of TTS the so-called "bowl formation" effect can be avoided, which ensures rational and cost-effective production poses.

According to the invention the object is achieved by a transdermal therapeutic system (TTS), in particular an active substance-containing plaster, which has the features mentioned in the preamble of claim 1, and the back layer of which has the following features:

  • - It is made with a unidirectional elastic material an elasticity of at least 20% and at most 150% educated,
  • - It is made of a material that is more than 90% mi is not biodegradable,
  • - it contains a material from the group of polyethylenes, Polypropylene and polyester and the polyalkylene terephthalate late,
  • - It has a water vapor permeability of at least 0.1 g / m 2 / h to 20 g / m 2 / h.

Preferred embodiments of the TTS according to the invention are Subject of the subclaims.

According to the invention, the TTS has a removable one Protective layer and an adhesive reservoir layer too a backing layer optionally also coated with adhesive on that a specially defined unidirectional elastic activity shows. The elasticity is in the invention TTS according to the ver used DIN standards 60000 and 61632 (April 1985) Right. These DIN standards originally apply to Ideal bandages; ver verifying the elasticity horizontal force expansion system is also used other materials can be used analogously. According to the invention in the TTS, the backing layer in only one direction, i.e. H. in Longitudinal or transverse direction elastic. Based on the longitudinal axis of the TTS is the transverse axis, which is at right angles to it lying axis. With a circular TTS, longitudinal and The transverse axis is naturally identical in length. In particular is the backing material used in the present invention unidirectionally longitudinally elastic.

In the other direction, the back layer is not ela pretty. "Non-elastic" means that when tested by No elasticity can be determined by hand. When measuring according to  DIN 61632 then the elasticity is below 20%. According to the invention, the elasticity lies in one name Lich the elastic direction - above 20%.

Because when making the patch the same thing from a laminate is punched out, it would in principle also be conceivable that the TTS at an angle to the longitudinal direction of the patch "unidi rectional "is elastic. Such an oblique elasticity is, however, the result of a superposition of elasticity in the transverse and in the longitudinal direction.

In the TTS according to the invention, a unidirectional ela used for the backing material, the Elasticity is less than 150%. In a preferred one Embodiment, the elasticity is in the range between 20 and 80%, particularly preferably in the range between 40 and 70%. Most preferred and therefore for the solution the object on which the invention is based advantageously testing is a material for the back layer, its elasti zity - always measured according to DIN 61632 - in the range between between 44 and 56%.

Preferred materials for the unidirectional elastic Backing layers are microbially non-degradable substances. The Ma material should be more than 90%, preferably more than 99% not be microbially degradable. The degradability can with usual methods known to the skilled worker are measured. The low degradability is particularly important with TTS, the should be worn longer on the skin. Because conditionally through the transpiration of the skin arises immediately below the skin area covered by the TTS is a microclimate, in which bacteria, fungi, spores etc. thrive on. Des half is low microbial degradability, especially re with longer wearing times, extremely advantageous. In which Backing material can be a fabric, a Trade fleece or a film. Covers the backing  Polymer, this is advantageously made of polyethylene, poly propylene or polyesters, especially polyalkylene tere phthalates selected.

Some polymeric materials for dis Called back layer. Cheap polymeric materials that above requirement of low microbial degradability are polyterephthalic diesters, which are produced by the Implementation of a starting material selected from ethylene glycol kol, 1,4-butanediol, 1,4-dihydroxymethylcyclohexane, tere phthalic acid, isophthalic acid, adipic acid, azelaic acid, Se bacic acid, dimethyl terephthalate, dimethyl azelaic acid ethyl ester, dimethyl sebacate, bisphenol A diglycid ester, n-decanedicarboxylic acid-1.10, polyethylene glycol and Po lybutylene glycol are available.

In the transdermal therapeutic sy according to the invention stem can be between the backing layer and the reservoir layer if another separation layer, e.g. B. to avoid of permeability to active substances. In this The case is the backing layer on the side facing the skin or the separation layer on the distal side as well pressure sensitive adhesive coated.

It is fine for the effectiveness of a TTS according to the invention stig when the back layer over all sides of the reservoir protrudes. This has the advantage that it is in the lateral direction there is no loss of active ingredient. It can also be invented TTS according to the invention then produced particularly inexpensively be, because the active ingredient-containing sections ge can be punched. In this way, expensive and environmentally harmful, waste residues containing active substance avoided.

The back layer of the TTS has a water vapor permeability of at least 0.1 g / m 2 / h, preferably from 1 to 20 g / m 2 / h. In the case of the use of a fleece or a fabric or a porous film, the porosity is in the range from 10% to 50%. "Porosity" means the area percentage of pores with an area of. 400 µm 2 on the respective reference surface. This relative pore area can be determined by measuring and counting the pores of any unexpanded reference area under the microscope or a thread counter.

If for the transdermal therapeutic according to the invention System (TTS) a tissue is used, so the back layer a warp thread number in the range of 300-350 before moves in the range of 310-330, and / or a weft count in the range of 100-140, preferably in the range of 120 to 130, each measured 10 cm of unstretched tissue.

The pressure-sensitive adhesive reservoir layer of the invention transdermal therapeutic system contains at least an active ingredient. This is preferably selected from the Group of psychotropic drugs, analgesics and hormones. As Hor Mon is particularly suitable for estradiol, as an analog tic buprenorphine. The psychopharmaceutical is preferably around a parasympathomimetic.

Possible parasympathomimetics are in particular:

  • 1. Choline ester, e.g. B. Acetylcholine, Bethanechol, Carbachol or methacholine,
  • 2. alkaloids, e.g. B. Arecolin and its derivatives, Pilocar pin code,
  • 3. Cholinesterase inhibitors, e.g. B. demecarium bromide, Distigmine bromide, neostigmine, physostigmine, Pyridostigmine bromide, galanthamine.

Of course, these substances can also be used in combination who are used. The content of active ingredient is in particular  special set so that when you remove the Patch comes to a so-called "tear-off effect". This Effect is explained in more detail below:

Does a TTS have a limited water vapor permeable back layer, e.g. B. a PET film can while wearing the TTS do not breathe water vapor from the skin at the application site. This water is stored in the skin. On the applica The location of the water is therefore higher than physiobio logically conditional. A skin resor difficult Beer product (such as buprenorphine) is placed in a depot be stored in the skin. Breathing when the TTS is torn off the skin suddenly absorbs water vapor.

By removing this water, the concentration suddenly rises tration of the drug over the saturation concentration as solvent is removed. A steady state will achieved by quickly emptying the skin depot. It therefore comes quickly due to the tearing off of the TTS Increased concentration of the active substance in plasma. For better Ren active ingredient utilization is the exploitation of the tear-off effect prefers. According to the invention, the concentration of Active ingredient adjusted so that the Ab tear effect comes into play.

The absolute amount of active ingredient content to achieve the tear-off effect cannot be defined as generally applicable ren. It varies from active ingredient to active ingredient and also depends depends on the embodiment of the TTS. The setting can however, by experts using routine experiments without unreasonable real effort. In the case of the buprenor phins the content is about 5-15 wt .-%.

The pressure-sensitive adhesive reservoir layer can also contain a water-absorbing polymer. In a preferred embodiment, the water-absorbing polymer is a polyvinylpyrrolidone. The polyvinylpyrrolidone preferably has a molecular weight in the range from 1 × 10 3 to 2 × 10 6 . Such polyvinylpyrrolidones include Kollidon®.

For special purposes, for example for use in Hospitals with lots of patients or for use in double-blind studies where drug-containing TTS with placebo TTS are compared, it is also preferred if the outward - i.e. away from the skin - side of the TTS in the back layer set off from the rest of the surface tes marker control element.

This element can be found in the structure or remaining egg properties, such as elasticity or porosity, of the rest distinguish part of the backing layer. By such a The marking control element can change the properties the backing layer can be set differentially. At for example, the elasticity of such an element be greater than the elasticity of the rest of the back layer. If such a marker control element is specially introduced in part of the backing layer, so lies its relative elasticity - in the event that this is desired - preferably in a range that is around 20% below or by 20% above the elasticity of the rest Part of the backing layer.

The marker control element can also serve to the individual TTS of each other with regard to their active substance content differentiate. This is preferably done by a colored marking, for example by a colored company the or strip. This is particularly beneficial if that TTS in one place, for example a hospital with many len patients, in large quantities in different doses must be kept ready.  

The transdermal therapeutic system according to the invention is particularly suitable for use as a multi-day supplement ster because of its specially tailored to this need a backing. In this respect, there is treatment in particular treatment of chronic pain or for treatment drug addiction.

The TTS according to the invention is carried out using conventional methods manufactured. Such a process generally includes the steps that from a presented ribbon-shaped lami nat, comprising the unidirectional elasti according to the invention back layer, an active ingredient layer and another removable protective layer, by punching the individual TTS getting produced.

In a preferred method of making the invented According to the TTS, the above steps are like this modified that with a submitted band-shaped laminate with a possibly adhesive, unidirectional ela static backing and removable protection layer in the longitudinal direction one behind the other pressure sensitive adhesive fabric reservoir sections are inserted, the back layer by punching and then in the spaces between the protective layer between the active substance reservoir sections is severed.

This special procedure has the advantage that it is under economic and also from an ecological point of view is very beneficial. By inserting the knit separately fabric reservoir sections is namely avoided that waste with - usually very expensive - active ingredient and must be disposed of costly. An analogous procedure is described in DE-B 41 10 027, in this regard explicit reference is made.  

The invention is based on a drawing and of an embodiment explained. The figures show ren:

Figure 1 shows the TTS according to the invention in plan view.

Fig. 2 shows the TTS of FIG. 1, cut along the positions II-II.

Fig. 1 shows schematically an inventive TTS in plan view. On the removable, in this case rectangular, protective layer ( 1 ) lies the back layer ( 5 ) coated with an active ingredient-free pressure sensitive adhesive. It has the shape of a rectangle with rounded corners. The punch line ( 1 a) outlines the shape of the backing layer ( 5 ). It runs outside the laminate of reservoir ( 2 ) and optional barrier or separating layer ( 3 ). Due to the course of the punching line, loss of active ingredient is avoided during punching. Within the back layer ( 5 ), the contours from the reservoir ( 2 ) and the optional barrier layer ( 3 ) can be seen.

In the illustrated TTS with a unidirectionally elastic backing layer ( 5 ), this protrudes beyond the laminate mentioned above on all sides. The reservoir preferably has a rectangular shape. The rectangular shape is therefore preferred, since active ingredient losses can thus be avoided when cutting the reservoir ( 2 ).

Fig. 2 is a cross section according to II-II of Fig. 1. For the sake of clarity, the layer thicknesses are exaggerated. The TTS has the reservoir ( 2 ), the removable protective layer ( 1 ) as well as the optionally available barrier layer ( 3 ) and another - in the case of the presence of a barrier layer ( 3 ) necessary - drug-free adhesive layer ( 4 ). In this embodiment shown, the above-mentioned laminate of the backing layer ( 5 ) and the active ingredient-free pressure-sensitive adhesive layer ( 4 ) protrudes on all sides.

example

To produce the unidirectional ela invention The back layer was a polyester fabric with the fol characteristics by means of the techni known to those skilled in the art ken manufactured.

In addition,
49.175 kg Durotak Type 387-2054 (48.3% solution)
4.450 kg of melted levulinic acid and
6.675 kg oleyl oleate
homogenized with stirring. Then 4.450 kg of Kollidon® 90F were added in portions. After dilution with 6,800 kg of ethanol, the mixture was stirred at 170-190 rpm for 5 hours. Then 4,450 kg of buprenorphine base, slurried in 4,500 kg of ethyl acetate, were added. The mixture was diluted with 4,500 kg of ethyl acetate. Kollidon® 90F is a polyvinylpyrrolidone preparation; BASF.

The mixture was stirred at 170 rpm for about 7 hours. On finally, there was a check for homogeneity. Was the Mass homogeneous, it was degassed with the stirrer switched off.

After homogenization, the adhesive was applied to egg ne siliconized polyester film spread. By The orga were dried at usually 35 ° C to 80 ° C African solvent removed. Then the La minat made of siliconized polyester film and buprenorphine containing pressure sensitive adhesive layer with a 23 µm thick second Polyester film covered.

The siliconized polyester film was removed from the active substance-containing laminate obtained in this way. Then 50 cm 2 large rectangles were punched out and the adhesive side was placed at 3 cm intervals on the siliconized side of a further 100 μm polyester protective film. The unidirectionally elastic polyester fabric - in this case also coated with pressure-sensitive adhesive - was placed over these reservoir sections. Elongated elastic plaster strips were then punched out. A wear test was carried out on n = 10 subjects using this TTS according to the invention.

Comparative Example 1

Instead of the unidirectionally elastic polyester fabric according to the invention, a bidirectionally elastic polyester fabric was used in this example. The extensibility of this fabric (longitudinal and transverse elongation) was 30%, measured in accordance with DIN 61632. The weight per unit area was 109 g / m 2 . The material was a polyethylene terephthalate. Otherwise, the TTS produced according to this comparative example corresponded to those of the example according to the invention.

Using the TTS according to this comparative example a wear test was also carried out on n = 10 subjects leads.

Comparative Example 2

TTS were produced in accordance with Example 1 and Comparative Example 1, except that instead of a unidirectionally elastic backing layer or a bidirectionally elastic backing layer, a rigid polyester film coated with adhesive (15 μm thickness) (Hostaphan® RN 15 , Hoechst AG) was used. In this case, too, a wear test was carried out on n = 10 test subjects using the TTS obtained in this way.

evaluation

The comparative wear test of the TTS according to Example 1, Comparative Example 1 and Comparative Example 2 gave the following result:

When using polyester film as the backing layer (comparative example 2 ), a foreign body sensation already occurred on the first day. Wrinkles developed on the second day and - starting on the third day - the TTS detached. The TTS according to Example 1 as well as that according to Comparative Example 1 was worn by all 10 test subjects without foreign body feeling, without impairing the adhesive force and also without skin irritation without problems for at least seven days. In terms of wearing comfort, the TTS according to Example 1 and the one are thus according to comparative example 1 approximately equivalent. However, in the manufacture of the TTS according to Comparative Example 1, complications in the manufacture occurred more than 50%, which were mainly due to the bowl formation effect.

Claims (8)

1. Transdermal therapeutic system, comprehensive
  • - a protective layer that can be removed from the skin before application,
  • a pressure-sensitive adhesive layer containing the active substance,
  • - a vapor-permeable backing layer which is impermeable to active substances,
characterized in that the backing layer has the following features:
  • it is made of a unidirectionally elastic material with an elasticity of at least 20% and at most 150%,
  • - it is made of a material that is more than 90% non-biodegradable,
  • it contains a material from the group of polyethylenes, polypropylenes and polyesters and polyalkylene terephthalate,
  • - It has a water vapor permeability of at least 0.1 g / m 2 / h to 20 g / m 2 / h.
2. Transdermal therapeutic system according to claim 1, characterized in that the backing layer with a fabric a number of warp threads in the range of 300 to 350 and one Number of weft threads in the range from 100 to 140 at 10 cm each has unstretched tissue.
3. Transdermal therapeutic system according to claim 1, characterized in that the backing is a warp number in the range from 310 to 330 and a number of weft threads in the Range from 120 to 130 with 10 cm unstretched fabric be.  
4. Transdermal therapeutic system according to one or several of claims 1 to 3, characterized in that the elastic material has an elasticity in the range of 20 to 80%, preferably in the range from 40 to 70% which preferably has in the range from 44 to 56%.
5. Transdermal therapeutic system according to one or several of claims 1 to 4, characterized in that the back layer extends beyond the reservoir on all sides.
6. Transdermal therapeutic system according to one or several of claims 1 to 5, characterized in that the back layer on the side facing the reservoir an adhesive layer is coated, and that between this Adhesive layer and the reservoir layer to a separation layer is ordered.
7. Transdermal therapeutic system according to one or several of claims 1 to 6, characterized in that the backing material is a polyterephthalic acid di is ester, preferably by reacting one of the Ethylene glycol, 1,4-butanediol, 1,4-dihydroxymethylcyclo hexane, terephthalic acid, isophthalic acid, adipic acid, aze Lainic acid, sebacic acid, dimethyl terephthalate, aze dimethyl lainate, dimethyl sebacate, bisphe nol-A-diglycide ester, n-decanedicarboxylic acid-1.10, polyethylene Group containing lenglycol and polybutylene glycol selected starting material available polyterephthalic acid is diol ester.
8. Transdermal therapeutic system according to one or more of claims 1 to 7, characterized in that the pressure-sensitive adhesive reservoir layer contains a water-absorbing polymer with a molecular weight in the range from 1 × 10 3 to 2 × 10 6 .
DE1997138855 1997-09-05 1997-09-05 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer Expired - Fee Related DE19738855C2 (en)

Priority Applications (1)

Application Number Priority Date Filing Date Title
DE1997138855 DE19738855C2 (en) 1997-09-05 1997-09-05 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer

Applications Claiming Priority (16)

Application Number Priority Date Filing Date Title
DE1997138855 DE19738855C2 (en) 1997-09-05 1997-09-05 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer
SI9830189T SI1009393T1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
EP19980948853 EP1009393B1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
DE1998503647 DE59803647D1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic rear layer
AT98948853T AT215364T (en) 1997-09-05 1998-08-21 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic rear layer
US09/486,266 US6814976B1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
PCT/EP1998/005321 WO1999012529A2 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
CA 2302601 CA2302601C (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
ES98948853T ES2175792T3 (en) 1997-09-05 1998-08-21 Transdermal administration system with adhesive contact reserve layer and unidirectional elastic superior layer.
DK98948853T DK1009393T3 (en) 1997-09-05 1998-08-21 Transdermal, therapeutic system with adhesive reservoir layer and backing layer which is elastic in one direction
AU95329/98A AU738033B2 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system with pressure-sensitive adhesive reservoir layer and unidirectionally elastic backing layer
JP2000510427A JP3847088B2 (en) 1997-09-05 1998-08-21 Percutaneous absorption therapy system comprising a storage pressure sensitive adhesive layer and a unidirectional elastic backing layer
KR10-2000-7002344A KR100515007B1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system comprising a reservoir-type pressure-sensitive adhesive layer and a back layer with uni-directional resilience
PT98948853T PT1009393E (en) 1997-09-05 1998-08-21 Transdermic therapeutic system with self-adhesive layer reservoir type and unidirectional elastic posterior layer
NO20001003A NO327605B1 (en) 1997-09-05 2000-02-28 Transdermal therapeutic system, process feed for the preparation and andvendelse this
US10/891,942 US7384651B2 (en) 1997-09-05 2004-07-15 Transdermal therapeutic system comprising a reservoir type pressure sensitive adhesive layer and a back layer with uni-directional resilience

Publications (2)

Publication Number Publication Date
DE19738855A1 DE19738855A1 (en) 1999-03-11
DE19738855C2 true DE19738855C2 (en) 2001-01-04

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DE1997138855 Expired - Fee Related DE19738855C2 (en) 1997-09-05 1997-09-05 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic back layer
DE1998503647 Expired - Lifetime DE59803647D1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic rear layer

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DE1998503647 Expired - Lifetime DE59803647D1 (en) 1997-09-05 1998-08-21 Transdermal therapeutic system with adhesive reservoir layer and unidirectional elastic rear layer

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US (2) US6814976B1 (en)
EP (1) EP1009393B1 (en)
JP (1) JP3847088B2 (en)
KR (1) KR100515007B1 (en)
AT (1) AT215364T (en)
AU (1) AU738033B2 (en)
CA (1) CA2302601C (en)
DE (2) DE19738855C2 (en)
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DE19738855A1 (en) 1999-03-11
PT1009393E (en) 2002-09-30
NO327605B1 (en) 2009-08-31
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EP1009393A2 (en) 2000-06-21
AU9532998A (en) 1999-03-29
US6814976B1 (en) 2004-11-09
KR20010023691A (en) 2001-03-26
AU738033B2 (en) 2001-09-06
NO20001003D0 (en) 2000-02-28
DE59803647D1 (en) 2002-05-08
WO1999012529A3 (en) 1999-05-27
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SI1009393T1 (en) 2002-10-31
EP1009393B1 (en) 2002-04-03
US20040253301A1 (en) 2004-12-16
WO1999012529A2 (en) 1999-03-18
CA2302601C (en) 2006-06-13
CA2302601A1 (en) 1999-03-18
AT215364T (en) 2002-04-15
JP2001515856A (en) 2001-09-25
US7384651B2 (en) 2008-06-10
KR100515007B1 (en) 2005-09-14
ES2175792T3 (en) 2002-11-16

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